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MeSH Disease

HGNC Genes

SARS-CoV-2 proteins

ProteinN (6)

ProteinS (5)

ORF8 (1)

ORF1a (1)

ORF1ab (1)


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SARS-CoV-2 Proteins
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    Ultrastructural insight into SARS-CoV-2 attachment, entry and budding in human airway epithelium

    Authors: Andreia L Pinto; Ranjit K Rai; Jonathan C Brown; Paul Griffin; James R Edgar; Anand Shah; Aran Singanayagam; Claire Hogg; Wendy S Barclay; Clare E Futter; Thomas Burgoyne

    doi:10.1101/2021.04.10.439279 Date: 2021-04-11 Source: bioRxiv

    Ultrastructural studies of SARS-CoV-2 infected MESHD cells are crucial to better understand the mechanisms of viral entry and budding within host cells. Many studies are limited by the lack of access to appropriate cellular models. As the airway epithelium is the primary site of infection it is essential to study SARS-CoV-2 infection MESHD of these cells. Here, we examined human airway epithelium, grown as highly differentiated air-liquid interface cultures and infected with three different isolates of SARS-CoV-2 including the B.1.1.7 variant (Variant of Concern 202012/01) by transmission electron microscopy and tomography. For all isolates, the virus infected ciliated but not goblet epithelial cells. Two key SARS-CoV-2 entry molecules, ACE2 HGNC and TMPRSS2 HGNC, were found to be localised to the plasma membrane including microvilli but excluded from cilia. Consistent with these observations, extracellular virions were frequently seen associated with microvilli and the apical plasma membrane but rarely with ciliary membranes. Profiles indicative of viral fusion at the apical plasma membrane demonstrate that the plasma membrane is one site of entry where direct fusion releasing the nucleoprotein PROTEIN-encapsidated genome occurs. Intact intracellular virions were found within ciliated cells in compartments with a single membrane bearing S glycoprotein PROTEIN. Profiles strongly suggesting viral budding from the membrane was observed in these compartments and this may explain how virions gain their S glycoprotein PROTEIN containing envelope.

    Evaluation of SARS-CoV-2 neutralization assays for antibody monitoring in natural infection and vaccine trials

    Authors: Anton M Sholukh; Andrew Fiore-Gartland; Emily S Ford; Yixuan Hou; Longping Victor Tse; Florian A Lempp; Hanna Kaiser; Russell Saint Germain; Emily Bossard; Jia Jin Kee; Kurt Diem; Andrew B Stuart; Peter B Rupert; Chance Brock; Matthew Buerger; Margaret K Doll; April Kaur Randhawa; Leonidas Stamatatos; Roland K Strong; Colleen McLaughlin; Keith R. Jerome; Ralph S. Baric; David Montefiori; Lawrence Corey

    doi:10.1101/2020.12.07.20245431 Date: 2020-12-08 Source: medRxiv

    Determinants of protective immunity against SARS-CoV-2 infection MESHD require the development of well-standardized, reproducible antibody assays to be utilized in concert with clinical trials to establish correlates of risk and protection. This need has led to the appearance of a variety of neutralization assays used by different laboratories and companies. Using plasma samples from COVID-19 MESHD convalescent individuals with mild-to-moderate disease from a localized outbreak in a single region of the western US, we compared three platforms for SARS-CoV-2 neutralization: assay with live SARS-CoV-2, pseudovirus assay utilizing lentiviral (LV) and vesicular stomatitis virus MESHD ( VSV MESHD) packaging, and a surrogate ELISA test. Vero, Vero E6, HEK293T cells expressing human angiotensin converting enzyme 2 HGNC ( hACE2 HGNC), and TZM-bl cells expressing hACE2 HGNC and transmembrane serine protease 2 ( TMPRSS2 HGNC) were evaluated. Live-virus and LV-pseudovirus assay with HEK293T cells showed similar geometric mean titers (GMTs) ranging 141-178, but VSV MESHD-pseudovirus assay yielded significantly higher GMT (310 95%CI 211-454; p < 0.001). Fifty percent neutralizing dilution (ND50) titers from live-virus and all pseudovirus assay readouts were highly correlated (Pearson r = 0.81-0.89). ND50 titers positively correlated with plasma concentration of IgG against SARS-CoV-2 spike PROTEIN and receptor binding domain (RBD) (r = 0.63-0.89), but moderately correlated with nucleoprotein PROTEIN IgG (r = 0.46-0.73). There was a moderate positive correlation between age and spike (Spearmans rho=0.37, p=0.02), RBD (rho=0.39, p=0.013) and nucleoprotein PROTEIN IgG (rho=0.45, p=0.003). ND80 showed stronger correlation with age than ND50 (ND80 rho=0.51 (p=0.001), ND50 rho=0.28 (p=0.075)). Our data demonstrate high concordance between cell-based assays with live and pseudotyped virions.

    Paradoxical effects of cigarette smoke and COPD MESHD on SARS-CoV2 infection MESHD and disease

    Authors: Michael Tomchaney; Marco Contoli; Jonathan Mayo; Simonetta Baraldo; Shuaizhi Li; Carly Cabel; David Bull; Scott Lick; Joshua Malo; Steve Knoper; Samuel Kim; Judy Tram; Joselyn Rojas Quintero; Monica Kraft; Julie Ledford; Fernando D Martinez; Curtis Thorne; Farrah Kheradmand; Samuel K Campos; Alberto Papi; Francesca Polverino

    doi:10.1101/2020.12.07.413252 Date: 2020-12-07 Source: bioRxiv

    IntroductionHow cigarette smoke (CS) and chronic obstructive pulmonary disease MESHD ( COPD MESHD) affect severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection MESHD and severity is controversial. We investigated the protein and mRNA expression of SARS-CoV-2 entry receptor ACE2 HGNC and proteinase TMPRSS2 HGNC in lungs from COPD MESHD patients and controls, and lung tissue from mice exposed acutely and chronically to CS. Also, we investigated the effects of CS exposure on SARS-CoV-2 infection MESHD in human bronchial epithelial cells. MethodsIn Cohort 1, ACE2 HGNC-positive cells were quantified by immunostaining in FFPE sections from both central and peripheral airways. In Cohort 2, we quantified pulmonary ACE2 HGNC protein levels by immunostaining and ELISA, and both ACE2 HGNC and TMPRSS2 HGNC mRNA levels by RT-qPCR. In C57BL/6 WT mice exposed to air or CS for up to 6 months, pulmonary ACE2 protein levels were quantified by triple immunofluorescence staining and ELISA. The effects of CS exposure on SARS-CoV-2 infection MESHD were evaluated after 72hr in vitro infection of Calu-3 cells. After SARS-CoV-2 infection MESHD, the cells were fixed for IF staining with dsRNA-specific J2 monoclonal Ab, and cell lysates were harvested for WB of viral nucleocapsid (N) protein PROTEIN. Supernatants (SN) and cytoplasmic lysates were obtained to measure ACE2 HGNC levels by ELISA. ResultsIn both human cohorts, ACE2 HGNC protein and mRNA levels were decreased in peripheral airways from COPD MESHD patients versus both smoker and NS controls, but similar in central airways. TMPRSS2 HGNC levels were similar across groups. Mice exposed to CS had decreased ACE2 protein levels in their bronchial and alveolar epithelia MESHD versus air-exposed mice exposed to 3 and 6 months of CS. In Calu3 cells in vitro, CS-treatment abrogated infection to levels below the limit of detection. Similar results were seen with WB for viral N protein PROTEIN, showing peak viral protein synthesis at 72hr. ConclusionsACE2 levels were decreased in both bronchial and alveolar epithelial MESHD cells from uninfected COPD MESHD patients versus controls, and from CS-exposed versus air-exposed mice. CS-pre-treatment did not affect ACE2 levels but potently inhibited SARS-CoV-2 replication in this in vitro model. These findings urge to further investigate the controversial effects of CS and COPD MESHD on SARS-CoV2 infection MESHD.

    Understanding Structural Malleability of the SARS-CoV-2 Proteins and their Relation to the Comorbidities

    Authors: Sagnik Sen; Ashmita Dey; Sanghamitra Bandyopadhyay; Ujjwal Maulik; Vladimir Uversky

    doi:10.21203/rs.3.rs-82352/v1 Date: 2020-09-23 Source: ResearchSquare

    Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), a causative agent of the coronavirus disease MESHD ( CoVID-19 MESHD), is a part of the β-coronaviridae family. In comparison with two other members of this family of coronaviruses infecting humans ( SARS-CoV and Middle East Respiratory Syndrome MESHD ( MERS MESHD) CoV), SARS-CoV-2 showed the most severe effects on the entire Earth population causing world-wide CoVID-19 pandemic MESHD. SARS-CoV-2 contains five major protein classes, such as four structural proteins (Nucleocapsid (N PROTEIN), Membrane (M), Envelop (E), and Spike Glycoprotein PROTEIN (S)) and Replicase polyproteins (R), which are synthesized as two polyproteins ( ORF1a PROTEIN and ORF1ab PROTEIN) that are subsequently processed into 12 nonstructural proteins by three viral proteases. All these proteins share high sequence similarity with their SARS-CoV counterparts. Due to the severity of the current situation, most of the SARS-CoV-2-related research is focused on finding therapeutic solutions and the analysis of comorbidities during infection. However, studies on the peculiarities of the amino acid sequences of viral protein classes and their structure space analysis throughout the evolutionary time-frame are limited. At the same time, due to their structural malleability, viral proteins can be directly or indirectly associated with the dysfunctionality of the host cell proteins, which may lead to comorbidities during the infection and at the post infection stage. To fill these gaps, we conducted the evolutionary sequence-structure analysis of the viral protein classes to evaluate the rate of their evolutionary malleability. We also looked at the intrinsic disorder propensities of these viral proteins and confirmed that although they typically do not have long intrinsically disordered regions (IDRs), all of them have at least some levels of intrinsic disorder MESHD. Furthermore, short IDRs found in viral proteins are extremely effective and prioritize the proteins for host cell interactions, which may lead to host cell dysfunction. Next, the associations of viral proteins with the host cell proteins were studied, and a list of diseases which are associated with such host cell proteins was developed. Other than the usual set of diseases, we have identified some maladies, which may happen after the recovery from the infections. Comparison of the expression rates of the host cell proteins during the diseases suggested the existence of two distinct classes. First class includes proteins, which are directly associated with certain sets of diseases, where they have shared similar activities. Second class is related to the cytokine storm-mediated pro- inflammation MESHD (already known for its role in acute respiratory distress syndrome MESHD, ARDS MESHD), and neuroinflammation may trigger some of the neurological malignancies and neurodegenerative and neuropsychiatric diseases MESHD. Finally, since the transmembrane serine protease 2 ( TMPRSS2 HGNC), which is one of the leading proteins associated with the viral uptake, is an androgen-mediated protein, our study suggested that males and postmenopausal females can be more susceptible to the SARS-CoV-2 infection MESHD.

    Multi-Omics and Integrated Network Approach to Unveil Evolutionary Patterns, Mutational Hotspots, Functional Crosstalk and Regulatory Interactions in SARS-CoV-2

    Authors: Vipin Gupta; Shazia Haider; Mansi Verma; Kalaiarasan Ponnusamy; Md. Zubbair Malik; Nirjara Singhvi; Helianthous Verma; Roshan Kumar; Utkarsh Sood; Princy Hira; Shiva Satija; Rup Lal

    doi:10.1101/2020.06.20.162560 Date: 2020-06-20 Source: bioRxiv

    SARS-CoV-2 responsible for the pandemic of the Severe Acute Respiratory Syndrome MESHD resulting in infections and death of millions worldwide with maximum cases and mortality in USA. The current study focuses on understanding the population specific variations attributing its high rate of infections in specific geographical regions which may help in developing appropriate treatment strategies for COVID-19 MESHD COVID-19 MESHD pandemic. Rigorous phylogenetic network analysis of 245 complete SARS-CoV-2 genomes inferred five central clades named a (ancestral), b, c, d and e (subtype e1 & e2) showing both divergent and linear evolution types. The clade d & e2 were found exclusively comprising of USA strains with highest known mutations. Clades were distinguished by ten co-mutational combinations in proteins; Nsp3 HGNC, ORF8 PROTEIN, Nsp13, S, Nsp12, Nsp2 HGNC and Nsp6 generated by Amino Acid Variations (AAV). Our analysis revealed that only 67.46 % of SNP mutations were carried by amino acid at phenotypic level. T1103P mutation in Nsp3 HGNC was predicted to increase the protein stability in 238 strains except six strains which were marked as ancestral type; whereas com (P5731L & Y5768C) in Nsp13 were found in 64 genomes of USA highlighting its 100% co-occurrence. Docking study highlighted mutation (D7611G) caused reduction in binding of Spike proteins PROTEIN with ACE2 HGNC, but it also showed better interaction with TMPRSS2 HGNC receptor which may contribute to its high transmissibility in USA strains. In addition, we found host proteins, MYO5A HGNC, MYO5B HGNC & MYO5C HGNC had maximum interaction with viral hub proteins (Nucleocapsid PROTEIN, Spike & Membrane). Thus, blocking the internalization pathway by inhibiting MYO-5 HGNC proteins which could be an effective target for COVID-19 MESHD treatment. The functional annotations of the Host-Pathogen Interaction (HPI) network were found to be highly associated with hypoxia MESHD and thrombotic MESHD conditions confirming the vulnerability and severity of infection in the patients. We also considered the presence of CpG islands in Nsp1 HGNC and N proteins PROTEIN which may confers the ability of SARS-CoV-2 to enter and trigger methyltransferase activity inside host cell.

    SARS-CoV2 ( COVID-19 MESHD) Structural/Evolution Dynamicome: Insights into functional evolution and human genomics.

    Authors: Ruchir Gupta; Jacob Charron; Cynthia Stenger; Jared Painter; Hunter Steward; Taylor Cook; William Faber; Austin Frisch; Eric Lind; Jacob Bauss; Xiaopeng Li; Olivia Sirpilla; Xavier Soehnlen; Adam Underwood; David Hinds; Michele Morris; Neil Lamb; Joseph Carcillo; Caleb Bupp; Bruce Uhal; Surender Rajasekaran; Jeremy W Prokop

    doi:10.1101/2020.05.15.098616 Date: 2020-05-15 Source: bioRxiv

    The SARS-CoV-2 pandemic, starting in 2019, has challenged the speed at which labs perform science, ranging from discoveries of the viral composition to handling health outcomes in humans. The small ~30kb single-stranded RNA genome of Coronaviruses makes them adept at cross species spread and drift, increasing their probability to cause pandemics. However, this small genome also allows for a robust understanding of all proteins coded by the virus. We employed protein modeling, molecular dynamic simulations, evolutionary mapping, and 3D printing to gain a full proteome and dynamicome understanding of SARS-CoV-2. The Viral Integrated Structural Evolution Dynamic Database (VIStEDD) has been established (prokoplab.com/vistedd), opening future discoveries and educational usage. In this paper, we highlight VIStEDD usage for nsp6, Nucleocapsid (N PROTEIN), and Spike (S) surface glycoprotein. For both nsp6 and N we reveal highly conserved surface amino acids that likely drive protein-protein interactions. In characterizing viral S protein PROTEIN, we have developed a quantitative dynamics cross correlation matrix insight into interaction with the ACE2 HGNC/ SLC6A19 HGNC dimer complex. From this quantitative matrix, we elucidated 47 potential functional missense variants from population genomic databases within ACE2 HGNC/ SLC6A19 HGNC/ TMPRSS2 HGNC, warranting genomic enrichment analyses in SARS-CoV-2 patients. Moreover, these variants have ultralow frequency, but can exist as hemizygous in males for ACE2 HGNC, which falls on the X-chromosome. Two noncoding variants (rs4646118 and rs143185769) found in ~9% of African descent individuals for ACE2 HGNC may regulate expression and be related to increased susceptibility of African Americans to SARS-CoV-2. This powerful database of SARS-CoV-2 can aid in research progress in the ongoing pandemic.

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MeSH Disease
HGNC Genes
SARS-CoV-2 Proteins


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